RESUMO
The effect of a bacterial lysate complex IRS 19 on local and systemic manifestations of inflammation was studied in a rat model of aseptic lymphadenitis. Injection of λ-carrageenan into the cervical lymph node via surgical approach caused an increase in the thickness of the capsule, disturbances in histoarchitecture, the appearance of necrosis foci, histiocytosis of subcapsular and cerebral sinuses in the lymph node, as well as an increase in the level of TNFα in the blood serum and the number of circulating leukocytes and neutrophils. Course intranasal administration of bacterial lysate complex in this model dose-dependently reduced the level of these markers of the systemic inflammatory response and the severity of microstructural disorders in the affected lymph nodes. Thus, bacterial lysate complex after intranasal administration produces a systemic anti-inflammatory effect that goes beyond the respiratory tract.
Assuntos
Linfadenite , Animais , Extratos Celulares , Inflamação/tratamento farmacológico , Linfonodos/patologia , Linfadenite/tratamento farmacológico , Linfadenite/patologia , Neutrófilos/patologia , RatosRESUMO
INTRODUCTION: Combination antiretroviral therapy is currently the main component of treatment for human immunodeficiency virus (HIV) infected patients. At the same time, the high mutational potential of the virus and the frequency of side effects of existing drugs dictate the need for the development and preclinical study of new, more effective and safer compounds.The aim of the study is to evaluate the specific types of toxicity of a new non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RNA-dependent DNA revertase) (NNRTI) based on the substance 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil, a benzophenone derivative. MATERIAL AND METHODS: The study investigated reproductive toxicity, embryotoxicity, immunotoxicity, genotoxic (in micronucleus test in and comet assay) and allergenic properties of the test itemcompound. It was tested on three species of animals in two doses: the estimated therapeutic dose (1 TD) and its tenfold equivalent (10 TD). Taking into account the metabolic coefficients, the doses for rats (Rattus) were 9 and 90 mg/kg, for mice (Mus musculus), 21 and 210 mg/kg, and for guinea pigs (Cavia porcellus), 8 and 80 mg/kg, respectively. RESULTS AND DISCUSSION: According to the obtained results, a favorable safety profile of the tested compound was established. Negative effects on the immune system, reproductive function, the body of pregnant animals and the fetus were not observed, as well as the compound did not have genotoxic and allergenic properties. CONCLUSION: These data allows to consider the studied compound as a promising therapeutic candidate for the treatment of HIV-1 infection.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Animais , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/toxicidade , Cobaias , Infecções por HIV/tratamento farmacológico , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/farmacologia , Transcriptase Reversa do HIV/uso terapêutico , HIV-1/genética , Humanos , Lentivirus , Camundongos , DNA Polimerase Dirigida por RNA/farmacologia , DNA Polimerase Dirigida por RNA/uso terapêutico , Ratos , Retroviridae , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/toxicidade , Uracila/análogos & derivadosRESUMO
Routinely the influenza virus significantly contributes to the formation of the annual incidence of acute respiratory infections, with a peak in winter season. The high level of mutagenic potential of influenza viruses is a standard factor determining the complexity of the rational choice of pharmacotherapy. The upcoming epidemiological season 20202021 brings additional challenges for health care practitioners mediated by the widespread prevalence in the human population of a new infection caused by the SARS-CoV-2 virus affecting the respiratory system among many organs and systems. An adequate choice of pharmacotherapy tools should be based on high efficiency and safety of drugs, with a possible reduction in such negative factors as polypharmacy. This review includes comparative pharmacological characteristics of drugs with activity against RNA viruses, along with parameters of their clinical efficacy.